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Project description:Clinical infection caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually increasing and spreading across the world, and phage therapy is a viable application as an alternative to antibiotics. However, additional clinical application is still restricted by the phage resistance. In order to further explore the mechanism of phage resistance, particularly the difference between in vivo and in vitro. Here, we used a mouse intra-abdominal infection (IAI) model to evaluate the antibacterial properties of two lytic phages and further isolated and characterized phage-resistant mutants. Finally, we determined through genomic and transcriptomic analysis that most of the mutation sites in the resistant mutants were located in the capsular polysaccharides gene cluster. However, RM01 and RM12 developed phage resistance by downregulating capsular polysaccharide (CPS) and its transcriptional regulators without any mutations in the CPS gene. In summary, these findings provided further evidence in phage therapy, particularly in addressing the issue of CR-hvKP infections.
2025-09-18 | MTBLS12480 | MetaboLights
Project description:High-resolution single-cell RNA-seq reveals the immune landscape of hvKp-infected lungs
2023-12-26 | GSE220594 | GEO
Project description:Hypervirulent Klebsiella pneumoniae (hvKp) is a significant pathogen causing severe community-acquired infections, characterized by the presence of a virulence plasmid. The plasmid-encoded regulator of mucoid phenotype A (RmpA) activates the expression of capsule genes, resulting in a hypermucoviscosity phenotype strongly associated with increased virulence. RmpA features a LuxR DNA-binding domain and a signaling-responsive domain, typical of proteins that regulate multiple biological processes. However, the comprehensive regulatory mechanisms of RmpA in hvKp remain unclear. Herein, RNA-seq showed that RmpA activates carbohydrate metabolism pathways while repressing those related to DNA replication, ribosome metabolism, and biofilm formation. ChIP-seq further confirmed RmpA’s role as a global regulator that not only enhances capsule production by activating transcripts within the capsule locus, but also upregulates the expression of key genes involved in synthesizing capsule precursors. RmpA regulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type III fimbriae genes. In addition, Expression of RmpA in Escherichia coli induced global transcriptional changes, suggesting it functions as a global regulator across species. These findings position RmpA as a central regulator in hvKp, orchestrating metabolic pathways and phenotypic traits essential for virulence.
2025-01-14 | GSE286111 | GEO